Inflammation and cell death

5 Cardinal signs of inflammation

Redness, heat, swelling, pain, loss of motion

Mast cell function

Activator of inflammatory response. Degranulation releases mediators such as histamine that increase vasodilation and permeability of blood vessels

Neutrophils function

Primary cell type in acute inflammation. Removed debris and dead cells and phagocytosis of bacteria

Macrophages functions

Phagocytosis of pathogen and debris. Releases pro inflammatory cytokines

Platelets function

Blood clotting and release of inflammatory mediators

1. Margination and rolling

Neutrophils and monocytes (macrophages) move to endothelial lining of blood vessels and ‘roll’ along cell wall

2. Adhesion

Inflammatory cells adhere to lining of blood vessels. Endothelial cells of blood vessel retract and create gaps between them

3. Diapedesis

Cell moves between endothelial cells. Neutrophils will be followed by lymphocytes and monocytes

4. Chemotaxis

The movement of cells toward a chemical stimulus released by neutrophils, monocytes & injured tissue

Outcomes of acute inflammation

Resolution, scarring or fibrosis, or progression to chronic inflammation

Characteristics of chronic inflammation

1. Infiltration with macrophages, lymphocytes and plasma cells

2. Tissue destruction mediated by inflammatory cells

3. Repair involving formation of new blood vessels (angiogenesis) and fibrosis

Chronic inflammation: eosinophils

Found when inflammation is caused by parasites or by allergens

Chronic inflammation: Mast cells

Armed with IgE to specific antigens and participate in the allergic response and anaphylactic shock

Chronic inflammation: Fibroblasts

Restores connective tissue matrix by synthesising and remodelling collagen, creating scar tissue

Causative agent of acute inflammation

Pathogens, injured tissue

Causative agent of chronic inflammation

Persistent acute inflammation, non degradable pathogens, persistent foreign bodies or autoimmune reactions

Why are macrophages better for chronic inflammation?

Neutrophils in acute inflammation has a short half life. Macrophages are long lived, can multiply in tissue, and migrate from blood to tissue

‘Activation’ of macrophages in chronic inflammation

Increasing content of lysosomal enzymes, having a more active metabolism, and a greater ability to kill organisms

Atrophy

Decrease/shrinkage of cell size

Hypertrophy

Increase in cell size. Often due to increased work load

Hyperplasia

Increase in number of cells in a tissue or organ. Can be caused by hormonal stimulation or compensatory

Metaplasia

Differentiated cell of a certain type is replaced by another cell type, which may be less differentiated

Dysplasia

Abnormal changes in size, shape and organisation of mature cells. Not a true adaptive change

Sudden reperfusion of cell consequence

Oxygen free radicals: reactive oxygen species (ROS) superoxide and peroxide

Impact of oxygen and oxygen free radicals

Free radicals are formed during ATP production from partially reduced oxygen molecules called reactive oxygen species.

Reactive oxygen species components

Has an unpaired electron that makes the molecule unstable. Meaning it can donate or gain an electron

Impact of oxygen and oxygen free radicals

Lipid peroxidation (damage to cell membrane), alterations in proteins, alterations to DNA, mitochondrial damage